The ubiquitous distribution and promiscuous dispersion of plasmids among procaryote strains presents a major health threat exacerbated by current medical treatment of infectious and congenital disease. On the positive side, breakthroughs in theory and technique, primarily in molecular genetics, provide a window for resolution of these health problems, and in addition, offer entirely new practical advances in eucaryote gene analysis and therapy. The plasmid loci of genetic determinants, DNA cistrons, code the enzymes of peripheral metabolism of unique structures, both natural and synthetic, including the xenobiotics, therapeutic human medicine and plant protection. The soil procaryotes, complemented by a group of soil procaryotes so far largely unstudied, are essential to the recycling of nitrogen and carbon and to the provision of renewable feedstocks of commerce and agriculture. Current selective evolution of both plasmid and chromosomal genes depend strongly on the fertility factors and replicons, and their organization among host strains. In their number, homology, incompatibility, structural gene aggregates, and new combinations, reside the mechanisms to advance genetic theory and basic observations, and the solution to the practical problems, both in health care and industry. We have prepared by mutation and transposon insertion, numerous plasmid markers, and by transduction and transformation, as well as cloning, a selected group of fertility factors, resistance and metabolic markers. We have mapped a series of 50 to 100 megadalton plasmid genomes by restriction and heteroduplex analyses and now have turned to their cloning for analytical, as well as chemical enzyme mechanism and structure analyses. We are now able to isolate the 200 ion megadalton plasmids, transform and predictably clone relevant fragments of the genomes, and build in hosts of known genetic composition, fertile plasmids for chemical and molecular genetic analysis. Current research and that anticipated for the next fiscal year exploit our earlier advances and selective critical facets of this array of problems.